Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer
AbstractToll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal cancer (CRC) patients. We identified Toll-like receptor 1 (TLR1), TLR2, TLR4 and TLR8 gene expression levels and downstream gene, i.e., interleukin-6 (IL-6), IL-8, interferon-α (IFN-α) and myeloid differentiation primary-response protein-88 (MyD88), expression levels in CRC patients and in cancer cell lines. CRC tissues have higher TLR1, TLR2, TLR4, TLR8, IL-6 and IL-8 gene expression levels than do the normal colon mucosa (p < 0.05). TLR2 expression varied in different cell types (mucosa and lymphocytes). There was no difference in the MyD88 and IFN-α gene expression levels between cancerous and normal colon mucosa. CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence. CL075 (3M002) treatments can reduce the production of IL-8 in different cancer cell lines. The signaling pathway of TLRs in cancer tissue is different from that in normal cells; and is MyD88-independent. Higher expression levels of TLR1, TLR2, TLR 4 and TLR 8 mRNA were related to upregulation inflammatory cytokines IL-6 and IL-8 gene expression in tissue and to the upregulation of IL-6 in blood. The concentration of IL-6 in serum can be used as an indicator of the possibility of CRC recurrence. Treatment with 3M002 can reduce IL-6 production in vitro and may prevent CRC recurrence. Our findings provide evidence that TLR1, TLR2, TLR4 and TLR8 gene expression induce downstream IL-6 and IL-8 gene expression; detection of these expression levels can serve as a CRC marker. View Full-Text
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Lu, C.-C.; Kuo, H.-C.; Wang, F.-S.; Jou, M.-H.; Lee, K.-C.; Chuang, J.-H. Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer. Int. J. Mol. Sci. 2015, 16, 159-177.
Lu C-C, Kuo H-C, Wang F-S, Jou M-H, Lee K-C, Chuang J-H. Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer. International Journal of Molecular Sciences. 2015; 16(1):159-177.Chicago/Turabian Style
Lu, Chien-Chang; Kuo, Hsing-Chun; Wang, Feng-Sheng; Jou, Ming-Huey; Lee, Ko-Chao; Chuang, Jiin-Haur. 2015. "Upregulation of TLRs and IL-6 as a Marker in Human Colorectal Cancer." Int. J. Mol. Sci. 16, no. 1: 159-177.